All authors have read and approved the article. Y.K. participated in writing of the article, performance of research, and samples collection. A.B. participated in sample collection and performance of research. A.P.S. participated in sample collection and writing of the article. Y.J. performed data analysis and writing of the article. S. Alakhdhair participated in sample collection and writing of the article. S.C.O. participated in sample collection and writing of the article.
Background:Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the post biopsy period. In this study we evaluated the effect of KT biopsy on the kinetics of dd-cfDNA.Methods:We conducted a single arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within eight hours prior to the biopsy (pre-biopsy), within 20 minutes (hour 0), 2 hours (hour 2), and 24-48 hours (hours 24-48) after the biopsy. We evaluated the change in dd-cfDNA from the pre-biopsy time point to the following 3 time points after the biopsy.Results:At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared to the pre-biopsy score [Least square mean (LSM) estimate 0.4 (0.17, 0.63) and 0.39 (0.09, 0.68) respectively]. By 24-28 hours post biopsy there was no significant difference in log dd-cfDNA mean score compared to the pre-biopsy score [LSM estimate -0.21 (-0.6, 0.19)]. Conclusion:KT biopsy leads to an increase in dd-cfDNA after the procedure, however, this rise is transient and resolves by 24-48 hour after the biopsy. Providers can obtain dd-cfDNA level as soon as 48 hours post biopsy with high confidence that the levels have not been affected by the biopsy. In addition, our findings suggest possible non-traditional reasons for increase in dd-cfDNA such as mechanical reasons.
Kidney transplantation is the best treatment modality for end-stage kidney disease, leading to improvement in a patient’s quality and quantity of life. With significant improvements in short-term outcomes, prolonging long-term allograft and patient survival remain ongoing challenges. The ability to monitor allograft function, immune tolerance and predict rejection accurately would enable personalization and better prognostication during post-transplant care. Though kidney biopsy remains the backbone of transplant diagnostics, emerging biomarkers can help detecting kidney allograft injury early enough to prevent permanent damage and detect injury before it is clinically apparent. In this review, we summarize the recent biomarkers that have shown promise in the prediction of acute rejection with a focus on antibody-mediated rejection in kidney transplantation.
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